P1105: NEUROLOGIC INVOLVEMENT IN ADULTS WITH ROSAI-DORFMAN DISEASE: CLINICAL PRESENTATION AND OUTCOMES
Authors: Aldo Acosta Medina, Jithma Abeykoon, Jason Young, Ronald Go, Eli Diamond, Gaurav Goyal
Journal: HemaSphere (2023)

Topic: 18. Indolent and mantle-cell non-Hodgkin lymphoma - Clinical Background: Rosai-Dorfman disease (RDD) is a rare histiocytic neoplasm with demonstrated alterations in the MAPK pathway in up to 50% of patients. Neurologic involvement with RDD is rare but can pose serious morbidity and influence the quality of life adversely; however, the exact frequency, clinical characteristics, and outcomes of neurologic RDD are unknown. Aims: To characterize the clinical landscape and outcomes of patients with RDD and neurologic involvement. Methods: Retrospective study including all consecutive cases of histopathologically confirmed RDD diagnosed at one of two tertiary referral centers in the US and with involvement of neurologic structures (intracranial and spinal), excluding isolated ophthalmologic disease. Results: A total of 28 patients were included in this study. Median age at diagnosis was 49 years (IQR 37 – 49 years), 64.3% (n=18) were female, and 14.3% had mixed histiocytoses (n=2 each for Langerhans cell histiocytosis and Erdheim-Chester disease). MRI of brain and spine were available in 25 (89.3%) and 14 (50%) patients, respectively. Only 24 of the MRIs were performed prior to RDD diagnosis. Regarding disease extension, 8 cases (28.6%) had isolated neurologic disease, 4 (14.3%) had disease extension only to contiguous structures, and the remaining cases had multisystem disease. Sites of neurologic involvement included: dural-based lesions (64.3%, n=18), orbital/ocular (42.9%, n=12), epidural soft tissues (39.3%, n=11), hypothalamus/pituitary (10.7%, n=3), cerebellum/brainstem (7.1%, n=2), and spinal cord (7.1%, n=2). While most parenchymal involvement stemmed from expansion of dural-based lesions, isolated parenchymal disease was evident in 2 cases (7.1%). Most common neurologic symptoms included ataxia (32.1%, n=9), headache (25%, n=7), diplopia/decreased visual acuity (21.4%, n=6), and peripheral neuropathy (17.9%, n=5). Systemic symptoms referred in more than 10% of cases included: significant fatigue (n=9), weight loss (n=3), and diffuse arthralgias/myalgias (n=3). Next-generation sequencing was conducted in 22 patients (78.6%). Most common pathogenic variants identified included those in MAP2K1 (n=6, %), and KRAS (n=4, %). Details on identified variants are presented in Table 1. Fourteen patients (50%) received therapy with a MEK inhibitor (cobimetinib n=11, trametinib n=4) throughout their disease course, 7 and 13 of whom had MAPK pathway mutations and available response assessment at time of data cutoff, respectively. Overall response rate was 92.3% (PR n=9, CR n=3). Noticeably, all patients achieving a CR had a demonstrated MAPK pathway mutation, while the only non-responder did not. After a median follow up of 50 months (95%CI 34-66 months), 3 patient deaths had been observed with one patient development therapy-related AML. Summary/Conclusion: Neurologic RDD is rare and can involve a wide variety of structures within the cranium and spine, causing significant symptomatology. Targeted therapy with MEK inhibitor appears promising in these casesKeywords: Adult, Histiocytosis